Throughout this application, various publications are referenced by author and date. Full citations for these publications may be found listed alphabetically at the end of the specification immediately preceding the sequence listing. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein.
It has been established that oxidative stress is associated with the development of cataract and it is generally believed that H.sub.2 O.sub.2 is the major oxidant producing this stress (Spector, 1995). Therefore, it would be constructive to produce a compound that would effectively eliminate H.sub.2 O.sub.2 in biological materials. However, efforts to produce such compounds have only been partially successful. Utilizing, as a model, reduced glutathione (GSH), glutathione peroxidase (GSHPx), a selenoenzyme which degrades H.sub.2 O.sub.2, attempts have been made to develop synthetic GSHPx mimics. A number of such selenium centered mimics have been synthesized, such as Ebselen and 2,2'diselenobis (N,N dimethylamino)methyl benzene (Wendel, 1985; Wilson et al., 1989). While these compounds have considerable GSHPx like activity, they have been found to be toxic in the .mu.M (micromolar) range required for effective activity based on lens epithelial cell culture viability studies. Furthermore, GSHPx-1 (the major glutathione peroxidase) transgenic mice, where the lens GSHPx-1 activity has been increased 4 to 5 fold, were found to be no more effective than normal lenses in metabolizing H.sub.2 O.sub.2 (Spector et al., 1996). This was found to be due to the limiting activity of GSSG Red (oxidized glutathione reductase) which is required to maintain GSH, a cofactor for the enzyme. In contrast to the GSHPx-1 results, increasing catalase activity (another peroxide degrading enzyme) in transfected lens epithelial cell cultures significantly increased H.sub.2 O.sub.2 degradation and the cell's ability to withstand oxidative stress (Spector et al., 1996).